Depression in neurodegenerative diseases: Common mechanisms and current treatment options. (July 2019)

• Record Type: Journal Article
• Authors: Galts, Ciaran P.C.; Bettio, Luis E.B.; Jewett, David C.; Yang, Charles C.; Brocardo, Patricia S.; Rodrigues, Ana Lucia S.; Thacker, Jonathan S.; Gil-Mohapel, Joana
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 102(2019)
• Page Start: 56
• Page End: 84
• Publication Date: 2019-07
• Subjects: Alzheimer's disease -- Clinical study -- Depression -- Huntington's disease -- Neurodegeneration -- Parkinson's disease -- Preclinical study; Aβ β-amyloid -- AD Alzheimer's disease -- APOE4 apolipoprotein E4 -- BAC bacterial artificial chromosome -- BDNF brain derived neurotrophic factor -- CAG cytosine–adenosine–guanine -- CBT cognitive behavioral therapy -- ChEI cholinesterase inhibitors -- CREB cAMP response element binding protein -- CRH corticotropin-releasing hormone -- CSF cerebrospinal fluid -- DAT dopamine transporter -- DBS deep brain stimulation -- DSM diagnostics and statistics manual of mental disorders -- FGF-2 fibroblast growth factor-2 -- fMRI functional magnetic resonance imaging -- GABA γ-aminobutiric acid -- HADS Hospital Anxiety and Depression Scale -- HAM-D Hamilton Rating Scale for Depression -- HD Huntington's disease -- HPA hypothalamic–pituitary–adrenal -- HPG hypothalamic–pituitary–gonadal -- IGF-1 insulin-like growth factor-1 -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- L-DOPA L-dihydroxyphenylalanine -- LTD long-term depression -- LTP long-term potentiation -- MAPK mitogen-activated protein kinase -- MDD major depressive disorder -- mHTT mutant huntingtin -- MAO monoamine oxidase -- MAOI monoamine oxidase inhibitor -- MRI magnetic resonance imaging -- NGF nerve growth factor -- NMDA N-methyl-D-aspartate -- NO nitric oxide -- PD Parkinson's disease -- PET positron emission tomography -- polyQ polyglutamine -- PSEN presenilin -- RAGE receptor for advanced glycation endproducts -- RCT randomized controlled trial -- SNRI selective noradrenaline reuptake inhibitor -- SSRI selective serotonin reuptake inhibitor -- TCA tricyclic antidepressant -- TLR Toll-like receptor -- TNF-α tumor necrosis factor-α -- TrkB tropomyosin receptor kinase B -- UHDR Unified Huntington's disease rating scale -- VEGF vascular endothelial growth factor -- YAC yeast artificial chromosome -- 5-HTT serotonin transporter -- 5-HTTLPR serotonin transporter polymorphism; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2019.04.002
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Major depressive disorder is commonly associated with AD, PD, and HD. Similar neurobiological changes contribute to the neuropathology of these diseases. AD, PD, HD and MDD are associated with cerebral structural and functional changes. Current antidepressants are not effective in treating MDD in AD, PD, and HD. New antidepressants are warranted to improve quality of life in AD, PD, and HD. Abstract: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a major cause of disability worldwide. This neurological condition is commonly associated with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), and has a significant impact on the increasing burden of these neuropathologies. Over the past decades, some of the pathophysiological and molecular mechanisms that contribute to these diseases have been elucidated and these findings indicate that, despite presenting distinct features, there are several similarities between the neurobiological alterations that lead to MDD and neurodegeneration in AD, PD, and HD. For instance, disturbances in monoaminergic transmission and the hypothalamic–pituitary–adrenal (HPA) axis, increased oxidative and neuroinflammatory events, and impaired trophic support are thought to contribute to neuronal atrophy and death in all these diseases. In addition, neuroimaging findings have helped elucidate the structural and functional changes implicated in the relationship between depression and neurodegeneration, thus establishing a neuroanatomical signature to explain, at least in part, the comorbidity between MDD and AD, PD, and HD. The present review summarizes these findings and the current evidence regarding the effectiveness of common antidepressant therapies for the treatment of MDD in patients with these neurodegenerative diseases. This population is particularly vulnerable to the drawdowns of conventional antidepressant therapy (namely inadequate response and high risk of side effects), and the development of emerging therapeutic approaches to treat MDD in patients with AD, PD, and HD is thus of paramount importance to improve the quality of life of these individuals.